The interaction and inhibition of muscle lactate dehydrogenase by the alkaloid caffeine

Biochem Biophys Res Commun. 1985 Mar 29;127(3):1057-65. doi: 10.1016/s0006-291x(85)80052-8.

Abstract

Kinetic analysis showed that the alkaloid caffeine is a competitive inhibitor of the enzyme lactate dehydrogenase with respect to substrate pyruvate, and a non-competitive inhibitor with respect to the coenzyme NADH. The inhibitor constant Ki is 0,54 mM. Scatchard analysis determined the dissociation constant for a single independent binding site of the ternary lactate dehydrogenase - NADH - caffeine complex (KE-NADH-CAFFEINE) and the number of binding sites to be 0,14 mM and 3,83 respectively. Caffeine binds to a hydrophobic domain in the substrate binding site. Alternate nucleophilic - electrophilic functionalities within the inhibitor molecule are proposed to be the fundamental reason for the inhibition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites
  • Binding, Competitive
  • Caffeine / metabolism
  • Caffeine / pharmacology*
  • Kinetics
  • L-Lactate Dehydrogenase / antagonists & inhibitors*
  • L-Lactate Dehydrogenase / metabolism
  • Muscles / enzymology*
  • NAD / metabolism
  • Pyruvates / metabolism
  • Pyruvic Acid
  • Rabbits

Substances

  • Pyruvates
  • NAD
  • Caffeine
  • Pyruvic Acid
  • L-Lactate Dehydrogenase